Methotrexate induced liver fibrosis is over estimated as assessed by transient elastography, acoustic radiation force impulse and serum markers

Abstract

Background and study aims: Noninvasive assessment of liver fibrosis is critical for monitoring rheumatoid arthritis (RA) patients undergoing methotrexate (MTX). This study aimed to detect subclinical liver fibrosis induced by MTX assessed using FIB-4, APRI, transient elastography (TE), and acoustic radiation force impulse (ARFI) elastography.

Patients and methods: This retrospective cohort study enrolled 120 RA patients: 60 patients received MTX, and 60 received a combination of MTX and leflunomide (LEF). Liver fibrosis assessment was conducted using FIB-4, APRI, TE, and ARFI at the time of enrollment. Pretreatment FIB-4 and APRI were calculated retrospectively.

Results: Serum transaminase levels remained within normal ranges in both groups regardless of treatment or MTX duration. The DAS 28 score indicated that the patients were in remission at the study time. At baseline (prior to MTX administration), 114 patients (95 %) exhibited low fibrosis risk according to FIB-4, whereas 6 patients (5 %) were classified as intermediate risk. APRI indicated that 117 patients(97.5 %) exhibited non-significant fibrosis, whereas 3 (2.5 %) presented with significant fibrosis. Upon enrollment, there was a significant increase in FIB-4 scores compared to the baseline in both groups (0.56 vs. 0.72; P = 0.0002 and 0.65 vs. 0.76; P < 0.001). However, values remained within non-significant ranges. The LEF and MTX combination significantly increased APRI (0.35 vs. 0.37; P = 0.006) without reaching thresholds for significant fibrosis. TE and ARFI indicated non-significant fibrosis (F0-F1) in 116 patients (96.7) (58 per group) and moderate fibrosis (F2) in 4 patients (3.3 %). The duration of MTX treatment emerged as a significant predictor of liver fibrosis, albeit mild, as demonstrated by logistic regression analysis (OR 1.15, P = 0.008).

Conclusion: The assessment of MTX-induced liver fibrosis in RA patients, usingTE, ARFI, and serum markers, appears to be overestimated. Transaminases did not serve as predictors of liver disease or fibrosis severity in RApatients undergoing MTXtreatment.

Keywords: Acoustic radiation force impulse (ARFI) elastography; Leflunomide; Liver fibrosis; Methotrexate (MTX); Noninvasive assessment; Rheumatoid Arthritis (RA); Transient Elastography (TE).